β-Lactams and β-Lactamase Inhibitors: An Overview
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β-Lactams are the most widely used class of antibiotics. Since the discovery of benzylpenicillin in the 1920s, thousands of new penicillin derivatives and related β-lactam classes of cephalosporins, cephamycins, monobactams, and carbapenems have been discovered. Each new class of β-lactam has been developed either to increase the spectrum of activity to include additional bacterial species or to address specific resistance mechanisms that have arisen in the targeted bacterial population. Resistance to β-lactams is primarily because of bacterially produced β-lactamase enzymes that hydrolyze the β-lactam ring, thereby inactivating the drug. The newest effort to circumvent resistance is the development of novel broad-spectrum β-lactamase inhibitors that work against many problematic β-lactamases, including cephalosporinases and serine-based carbapenemases, which severely limit therapeutic options. This work provides a comprehensive overview of β-lactam antibiotics that are currently in use, as well as a look ahead to several new compounds that are in the development pipeline.
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Resistance mechanisms spread rapidly via horizontal gene transfer.
“These resistance mechanisms spread rapidly via horizontal gene transfer, turning once-treatable pathogens into stubborn clinical challenges.”
From The penicillin revolution and the role of the forgotten pioneer Vincenzo Tiberio (1869-1915): discovery, development and legacy. (2025) · cites this paper as [13]
The β-Lactam Resistance: Concluding Remarks section (page unavailable) says that transferable β-lactamases travel on mobile elements among species and that high-level resistance can become a major clinical problem. It does not establish that these mechanisms spread rapidly, and it does not describe all the resistance mechanisms it lists as horizontally transferable. (LLM, conf=0.85)
Experimental — accuracy not yet measuredWidespread and indiscriminate antibiotic use created intense selective pressures that favored survival of resistant bacterial strains.
“Widespread and often indiscriminate use—in clinical settings, agriculture, animal husbandry, and even household products—created intense selective pressures that favored the survival of resistant bacterial strains.”
From The penicillin revolution and the role of the forgotten pioneer Vincenzo Tiberio (1869-1915): discovery, development and legacy. (2025) · cites this paper as [13]
The β-Lactam Resistance: Concluding Remarks section (page not provided) links increasing β-lactam resistance to widespread therapeutic dependence on those antibiotics. It does not address indiscriminate use, agriculture, animal husbandry, or household products, and it does not explicitly describe the selective-pressure mechanism attributed to it. (LLM, conf=0.86)
Experimental — accuracy not yet measuredBacterial production of β-lactamases hydrolyzes the β-lactam ring of penicillin and renders it ineffective.
“One of the earliest and most formidable forms of resistance was the bacterial production of β-lactamases, enzymes capable of hydrolyzing the β-lactam ring of penicillin and rendering it ineffective [13].”
From The penicillin revolution and the role of the forgotten pioneer Vincenzo Tiberio (1869-1915): discovery, development and legacy. (2025) · cites this paper as [13]
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Cited by
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Zhao, Y., Jaber, V., & Lukiw, W. J. (2017) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2017.00318 · Cited by 379 · see citing works
Bacterial proteases, untapped antimicrobial drug targets
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- Authors
- Bush, K., & Bradford, P. A.
- Affiliations
- Indiana University Bloomington (US)
- AstraZeneca (United States) (US)
- Venue
- Cold Spring Harbor Perspectives in Medicine
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2016-06-21
- Volume
- 6
- Issue
- 8
- Pages
- a025247
- ISSN
- 2157-1422 (ISSN-L)
- PMC
- PMC4968164
- OpenAlex
- W2463871935
- Cited by
- 1,412
- References
- 1
- Citations by year
- 2026: 282 · 2025: 253 · 2024: 215 · 2023: 165 · 2022: 137 · 2021: 144 · 2020: 98 · 2019: 56 · 2018: 26 · 2017: 31 · 2016: 4
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cold Spring Harbor Perspectives in Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Antibiotic Resistance in Bacteria
- Physical Sciences › Chemistry › Organic Chemistry › Synthesis of β-Lactam Compounds
- Health Sciences › Medicine › Pharmacology › Antibiotics Pharmacokinetics and Efficacy
- Keywords
- beta-lactam antibiotics, beta-lactamase inhibitors, penicillin, cephalosporins, cephamycins, monobactams, carbapenems, antibiotic resistance, beta-lactamase, cephalosporinase, drug discovery pipeline
- MeSH terms
- Cephalosporins, Humans, Monobactams, Penicillins, Carbapenems, beta-Lactam Resistance, History, 20th Century, History, 21st Century, beta-Lactamase Inhibitors
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